The Friend strain of the spleen focus-forming virus (SFFV), a replication-defective murine retrovirus, induces a rapid proliferation of erythroid precursor cells when it is injected as a pseudotype into succeptible mice. Two proteins encoded by SFFV have been identified, a gag gene-related protein and an env gene-related protein, gp52. In order to demonstrate which area(s) of the genome is responsible for the induction of disease, a genetic analysis of this virus has been performed. The gp52 protein is expressed in fibroblast cells after transfection and rescue of biologically active, molecularly cloned SFFV DNA. Evidence using two molecularly cloned subgenomic fragments of SFFV DNA and cloned in vitro mutagenized SFFV DNA indicates that the sequence necessary for the erythroproliferative disease and those encoding the gp52 are present in the same part of the viral genome; thus demonstrating that the gp52 is required for induction of the disease.